Thyroid nodules and differentiated thyroid cancer: update on the Brazilian consensus

Thyroid nodules are frequent findings, especially when sensitive imaging methods are used. Although thyroid cancer is relatively rare, its incidence is increasing, particularly in terms of small tumors, which have an uncertain clinical relevance. Most patients with differentiated thyroid cancer exhibit satisfactory clinical outcomes when treatment is appropriate, and their mortality rate is similar to that of the overall population. However, relapse occurs in a considerable fraction of these patients, and some patients stop responding to conventional treatment and eventually die from their disease. Therefore, the challenge is how to identify the individuals who require more aggressive disease management while sparing the majority of patients from unnecessary treatments and procedures. We have updated the Brazilian Consensus that was published in 2007, emphasizing the diagnostic and therapeutic advances that the participants, representing several Brazilian university centers, consider most relevant in clinical practice. The formulation of the present guidelines was based on the participants' experience and a review of the relevant literature.

Fibrose congênita de reto inferior atípica com hipotonia muscular generalizada: relato de um caso

A case report of an atipical inferior rectus congenital fibrosis associated with a generalized muscular hypotonia is presented. It shows mild hipotropia with a normal visual acuity and binocularity in infraversion position contrasting with the severe hipotropia and ambliopy found. The surgical procedure took these facts into consideration, so we performed a small retrocess of the muscle with the objective to correct the head position without changes in the reading position. The postoperative results were satisfactory.

Estudo comparativo de complicações durante o uso do aparelho de Herbst com cantiléver e com splint inferior de acrílico removível

OBJETIVO: verificar e comparar os tipos de complicações durante o tratamento com o aparelho de Herbst com cantiléver (CBJ) e com splint removível inferior. MÉTODOS: vinte e um pacientes tratados consecutivamente com o CBJ foram comparados a vinte e um pacientes tratados consecutivamente com o aparelho de Herbst com coroas de aço nos primeiros molares superiores e com splint de acrílico inferior removível. A idade inicial média para o grupo com CBJ foi de 12 anos e 3 meses, e para o grupo com splint foi de 11 anos e 3 meses. Ambos os grupos utilizaram o aparelho por um período de 12 meses. A partir da ficha clínica dos pacientes foi realizado um levantamento de ocorrências de complicações acontecidas durante o tratamento com os aparelhos de Herbst. RESULTADOS: o número total de ocorrências de complicações foi de 24 para o grupo com CBJ e de 53 para o grupo com splint. O teste de Mann-Whitney (p<0,05) demonstrou diferença significativa entre os dois tipos de tratamento em relação ao total de ocorrências de complicações durante o tratamento. A prevalência de pacientes que apresentaram alguma complicação durante o tratamento foi de 66,67% para os pacientes tratados com CBJ, e de 85,71% para os pacientes tratados com splint. CONCLUSÕES: o grupo com CBJ apresentou menor número de complicações durante o tratamento com o aparelho de Herbst. Em ambos os grupos, nenhum paciente apresentou individualmente um grande número de complicações. O aparelho CBJ é preferível ao modelo com splint de acrílico inferior removível, devido à economia de tempo clínico e laboratorial.

Extração de incisivo inferior: uma opção de tratamento ortodôntico

A exodontia de um incisivo inferior pode ser considerada uma opção valiosa na busca de excelência nos resultados ortodônticos para obtenção de máxima função, estética e estabilidade. O objetivo deste estudo foi reunir informações referentes às indicações, contraindicações, vantagens, desvantagens e estabilidade dos resultados obtidos nos tratamentos realizados com extração de um incisivo inferior. Essa opção de tratamento pode ser indicada em más oclusões com discrepância de volume dentário anterior devido a incisivos superiores estreitos e/ou incisivos inferiores largos. É contraindicada em más oclusões sem discrepância anterior ou com discrepâncias ocasionadas por incisivos superiores largos e/ou incisivos inferiores estreitos. A literatura sugere maior estabilidade pós-tratamento quando comparada com a opção de extrações de pré-molares. Além do diagnóstico cuidadoso, obtido com a colaboração do set-up, a habilidade e a experiência clínica do profissional são importantes para o sucesso dos resultados ortodônticos alcançados com essa opção de tratamento

Expression of SMAD proteins, TGF-beta/activin signaling mediators, in human thyroid tissues

OBJECTIVE: To investigate the expression of SMAD proteins in human thyroid tissues since the inactivation of TGF-β/activin signaling components is reported in several types of cancer. Phosphorylated SMAD 2 and SMAD3 (pSMAD2/3) associated with the SMAD4 induce the signal transduction generated by TGF-β and activin, while SMAD7 inhibits this intracellular signaling. Although TGF-β and activin exert antiproliferative roles in thyroid follicular cells, thyroid tumors express high levels of these proteins. MATERIALS AND METHODS: The protein expression of SMADs was evaluated in multinodular goiter, follicular adenoma, papillary and follicular carcinomas by immunohistochemistry. RESULTS: The expression of pSMAD2/3, SMAD4 and SMAD7 was observed in both benign and malignant thyroid tumors. Although pSMAD2/3, SMAD4 and SMAD7 exhibited high cytoplasmic staining in carcinomas, the nuclear staining of pSMAD2/3 was not different between benign and malignant lesions. CONCLUSIONS: The finding of SMADs expression in thyroid cells and the presence of pSMAD2/3 and SMAD4 proteins in the nucleus of tumor cells indicates propagation of TGF-β/activin signaling. However, the high expression of the inhibitory SMAD7, mostly in malignant tumors, could contribute to the attenuation of the SMADs antiproliferative signaling in thyroid carcinomas.

Equivalência conceitual, de itens e semântica da versão brasileira do instrumento Dysfunctional Voiding Scoring System (DVSS) para avaliação de disfunção do trato urinário inferior em crianças

Investiga-se a equivalência conceitual, de itens e semântica entre o instrumento Dysfunctional Voiding Scoring System (DVSS), utilizado para avaliar a disfunção funcional do trato urinário inferior em crianças, concebido em inglês e uma versão em português. Na primeira etapa realizou-se a avaliação da equivalência conceitual e de itens, seguida de duas traduções do instrumento original para o português. Na segunda etapa foram realizadas 63 entrevistas, com crianças de 3 a 10 anos e responsáveis, e modificação de itens segundo dificuldades de interpretação. Na terceira etapa foi realizada a retradução do instrumento em português para o inglês e avaliação da equivalência semântica. Na quarta etapa, a versão pré-teste foi aplicada em vinte duplas de crianças de 3 a 10 anos e responsáveis. Apresenta-se o instrumento em português com equivalência conceitual, de itens e semântica. Sugere-se que a aplicação do DVSS seja realizada por meio de entrevista por profissional treinado e não baseada em autopreenchimento como proposto no instrumento original.

O uso da acupuntura no auxílio à terapia da doença idiopática do trato urinário inferior dos felinos

Diferentes afecções podem acometer o trato urinário inferior dos felinos, acarretando sinais clínicos inespecíficos como: hematúria, disúria, polaquiúria, estrangúria, periúria ou obstrução, caracterizando a doença do trato urinário inferior dos felinos (DTUIF). Entretanto, em até 65% dos felinos acometidos, a etiologia é indeterminada, denominada de doença idiopática do trato urinário inferior dos felinos (DTUIF idiopática), que tem se mostrado como um desafio ao clínico veterinário, uma vez que não há diagnóstico específico ou terapia efetiva. Atualmente, tem sido estudado o papel da inflamação neurogênica da bexiga urinária secundária ao estresse, como etiologia da DTUIF idiopática. Há evidências científicas de que a acupuntura restaure a homeostase, reduza o estresse e, pela estimulação neural periférica, ative mecanismos endógenos de antinocicepção, regulando a liberação de mediadores dos mecanismos da dor e do processo inflamatório, como a substância P. O objetivo desta revisão bibliográfica foi descrever como a acupuntura pode ser um recurso na terapia da DTUIF idiopática, tendo como base a modulação da inflamação neurogênica da bexiga urinária e o controle do estresse desses gatos.

Metabolic syndrome and dietary components are associated with coronary artery disease risk score in free-living adults: a cross-sectional study

Background: Coronary artery disease (CAD) is among the main causes of death in developed countries, and diet and lifestyle can influence CAD incidence. Objective: To evaluate the association of coronary artery disease risk score with dietary, anthropometric and biochemical components in adults clinically selected for a lifestyle modification program. Methods: 362 adults (96 men, 266 women, 53.9 +/- 9.4 years) fulfilled the inclusion criteria by presenting all the required data. The Framingham score was calculated and the IV Brazilian Guideline on Dyslipidemia and Prevention of Atherosclerosis was adopted for classification of the CAD risks. Anthropometric assessments included waist circumference (WC), body fat and calculated BMI (kg/m(2)) and muscle-mass index (MMI kg/m(2)). Dietary intake was estimated through 24 h dietary recall. Fasting blood was used for biochemical analysis. Metabolic Syndrome (MS) was diagnosed using NCEP-ATPIII (2001) criteria. Logistic regression was used to determine the odds of CAD risks according to the altered components of MS, dietary, anthropometric, and biochemical components. Results: For a sample with a BMI 28.5 +/- 5.0 kg/m(2) the association with lower risk (<10% CAD) were lower age (<60 years old), and plasma values of uric acid. The presence of MS within low, intermediary, and high CAD risk categories was 30.8%, 55.5%, and 69.8%, respectively. The independent risk factors associated with CAD risk score was MS and uric acid, and the protective factors were recommended intake of saturated fat and fiber and muscle mass index. Conclusion: Recommended intake of saturated fat and dietary fiber, together with proper muscle mass, are inversely associated with CAD risk score. On the other hand, the presence of MS and high plasma uric acid are associated with CAD risk score.

Structural basis of GC-1 selectivity for thyroid hormone receptor isoforms

Background: Thyroid receptors, TRa and TR beta, are involved in important physiological functions such as metabolism, cholesterol level and heart activities. Whereas metabolism increase and cholesterol level lowering could be achieved by TR beta isoform activation, TRa activation affects heart rates. Therefore, beta-selective thyromimetics have been developed as promising drug-candidates for treatment of obesity and elevated cholesterol level. GC-1 [ 3,5-dimethyl-4-(4'-hydroxy- 3'-isopropylbenzyl)-phenoxy acetic acid] has ability to lower LDL cholesterol with 600-to 1400-fold more potency and approximately two-to threefold more efficacy than atorvastatin (Lipitor(C)) in studies in rats, mice and monkeys. Results: To investigate GC-1 specificity, we solved crystal structures and performed molecular dynamics simulations of both isoforms complexed with GC-1. Crystal structures reveal that, in TRa Arg228 is observed in multiple conformations, an effect triggered by the differences in the interactions between GC-1 and Ser277 or the corresponding asparagine (Asn331) of TR beta. The corresponding Arg282 of TR beta is observed in only one single stable conformation, interacting effectively with the ligand. Molecular dynamics support this model: our simulations show that the multiple conformations can be observed for the Arg228 in TR alpha, in which the ligand interacts either strongly with the ligand or with the Ser277 residue. In contrast, a single stable Arg282 conformation is observed for TR beta, in which it strongly interacts with both GC-1 and the Asn331. Conclusion: Our analysis suggests that the key factors for GC-1 selectivity are the presence of an oxyacetic acid ester oxygen and the absence of the amino group relative to T(3). These results shed light into the beta-selectivity of GC-1 and may assist the development of new compounds with potential as drug candidates to the treatment of hypercholesterolemia and obesity.

Lipid Metabolism in Subclinical Hypothyroidism: Plasma Kinetics of Triglyceride-Rich Lipoproteins and Lipid Transfers to High-Density Lipoprotein Before and After Levothyroxine Treatment

Background: Subclinical hypothyroidism (SCH) has been associated with atherosclerosis, but the abnormalities in plasma lipids that can contribute to atherogenesis are not prominent. The aim of this study was to test the hypothesis that patients with normocholesterolemic, normotriglyceridemic SCH display abnormalities in plasma lipid metabolism not detected in routine laboratory tests including abnormalities in the intravascular metabolism of triglyceride-rich lipoproteins, lipid transfers to high-density lipoprotein (HDL), and paraoxonase 1 activity. The impact of levothyroxine (LT4) treatment and euthyroidism in these parameters was also tested. Methods: The study included 12 SCH women and 10 matched controls. Plasma kinetics of an artificial triglyceride-rich emulsion labeled with radioactive triglycerides and cholesteryl esters as well as in vitro transfer of four lipids from an artificial donor nanoemulsion to HDL were determined at baseline in both groups and after 4 months of euthyroidism in the SCH group. Results: Fractional clearance rates of triglycerides (SCH 0.035 +/- 0.016 min(-1), controls 0.029 +/- 0.013 min(-1), p=0.336) and cholesteryl esters (SCH 0.009 +/- 0.007 min(-1), controls 0.009 +/- 0.009 min(-1), p=0.906) were equal in SCH and controls and were unchanged by LT4 treatment and euthyroidism in patients with SCH, suggesting that lipolysis and remnant removal of triglyceride-rich lipoproteins were normal. Transfer of triglycerides to HDL (SCH 3.6 +/- 0.48%, controls 4.7 +/- 0.63%, p=0.001) and phospholipids (SCH 16.2 +/- 3.58%, controls 21.2 +/- 3.32%, p=0.004) was reduced when compared with controls. After LT4 treatment, transfers increased and achieved normal values. Transfer of free and esterified cholesterol to HDL, HDL particle size, and paraoxonase 1 activity were similar to controls and were unchanged by treatment. Conclusions: Although intravascular metabolism of triglyceride-rich lipoproteins was normal, patients with SCH showed abnormalities in HDL metabolism that were reversed by LT4 treatment and achievement of euthyroidism.

TCF7L2 Polymorphism rs7903146 Is Associated with Coronary Artery Disease Severity and Mortality

Background: TCF7L2 polymorphisms have been consistently associated with type 2 diabetes mellitus in different populations and type 2 diabetes mellitus is a major risk factor for cardiovascular disease, especially coronary artery disease. This study aimed to evaluate the association between TCF7L2 polymorphism rs7903146 and coronary artery disease in diabetic and non-diabetic subjects. Methods and Results: two populations were studied in order to assess severity of coronary artery disease and cardiovascular events incidence. Eight-hundred and eighty nine subjects who were referred for cardiac catheterization for coronary artery disease diagnosis were cross-sectionally evaluated for coronary lesions (atherosclerotic burden) and 559 subjects from the MASS-II Trial were prospectively followed-up for 5 years and assessed for major cardiovascular events incidence. As expected, rs7903146 T allele was associated with diabetes. Although diabetic patients had a higher prevalence of coronary lesions, no association between TCF7L2 genotype and coronary lesions was found in this subgroup. However, non-diabetic individuals carrying the T allele were associated with a significantly higher frequency of coronary lesions than non-diabetic non-carriers of the risk allele (adjusted OR = 2.32 95% CI 1.27-4.24, p = 0.006). Moreover, presence of multi-vessel coronary artery disease was also associated with the CT or TT genotypes in non-diabetics. Similarly, from the prospective sample analysis, non-diabetics carrying the CT/TT genotypes had significantly more composite cardiovascular end-points events than CC carriers (p = 0.049), mainly due to an increased incidence of death (p = 0.004). Conclusions: rs7903146 T allele is associated with diabetes and, in non-diabetic individuals, with a higher prevalence and severity of coronary artery disease and cardiovascular events. name of registry site (see list below), registration number, trial registration URL in brackets.

Genetic Variants of Diabetes Risk and Incident Cardiovascular Events in Chronic Coronary Artery Disease

Objective: To determine whether information from genetic risk variants for diabetes is associated with cardiovascular events incidence. Methods: From the about 30 known genes associated with diabetes, we genotyped single-nucleotide polymorphisms at the 10 loci most associated with type-2 diabetes in 425 subjects from the MASS-II Study, a randomized study in patients with multi-vessel coronary artery disease. The combined genetic information was evaluated by number of risk alleles for diabetes. Performance of genetic models relative to major cardiovascular events incidence was analyzed through Kaplan-Meier curve comparison and Cox Hazard Models and the discriminatory ability of models was assessed for cardiovascular events by calculating the area under the ROC curve. Results: Genetic information was able to predict 5-year incidence of major cardiovascular events and overall-mortality in non-diabetic individuals, even after adjustment for potential confounders including fasting glycemia. Non-diabetic individuals with high genetic risk had a similar incidence of events then diabetic individuals (cumulative hazard of 33.0 versus 35.1% of diabetic subjects). The addition of combined genetic information to clinical predictors significantly improved the AUC for cardiovascular events incidence (AUC = 0.641 versus 0.610). Conclusions: Combined information of genetic variants for diabetes risk is associated to major cardiovascular events incidence, including overall mortality, in non-diabetic individuals with coronary artery disease.

Expression of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase 2 (TIMP-2) in medullary thyroid carcinoma: Prognostic implications

Background: Metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase 2 (TIMP-2) participate in the degeneration of the extracellular matrix and are associated with carcinogenesis. MMP-2 is one of the main metalloproteinases active in neoplasia and is a marker of the malignant phenotype. Since the biological behavior of medullary thyroid carcinoma (MTC) varies widely, the present study was undertaken to determine if there is a correlation between the clinical evolution of MTC and the immunohistochemically detected expression of these enzymes in thyroid surgical specimens containing MTC. If so, their expression would be a novel indicator of the prognosis of MTC. Methods: Thirty-seven patients with MTC who had undergone thyroid surgery were followed for an average of 73 months. Immunohistochemical staining for metalloproteinase-related enzymes was performed in surgical paraffin blocks. The clinical status of the patients after surgery and at the end of the study period was characterized to determine correlations between these and the immunohistochemical markers. A value of p < 0.05 was considered statistically significant. Results: At the end of the study period, 15 patients (40.5%) were alive and without evidence of MTC, 17 (45.9%) had persistent MTC, and 5 (13.5%) had a relapse of their neoplasia. Four patients (10.8%) died during the course of the study. There was a significant correlation (p = 0.0005) between the immunohistochemical staining for MMP-2 and the clinical condition of the patients at the end of the study period, and a correlation between the state of apparent cure compared to persistence of MTC after thyroid surgery (p = 0.0207). No significant correlations were observed between either TIMP-2 expression or immune marking of metastatic lymph nodes and the clinical variables studied. Conclusion: Immunohistochemical expression of MMP-2 in thyroid surgical specimens from patients with MTC is a novel indicator of the prognosis of this cancer.

Vascular Endothelial Growth Factor Expression in Invasive Papillary Thyroid Carcinoma

Background: The vascular endothelial growth factor (VEGF) is a major promoter of endothelial growth and migration. Some studies have shown a correlation between expression of this growth factor and prognosis in several cancers, including well-differentiated thyroid cancer. Aim: We studied VEGF expression, local invasiveness, and other prognostic factors in papillary thyroid carcinoma (PTC) to test the hypothesis that the expression of VEGF is correlated with the degree of invasion of PTC. Patients and Methods: Clinical and pathological data of 76 patients with PTC were retrospectively reviewed. Group 1 consisted of patients with gross locally invasive tumors, group 2 consisted of patients with only invasion of the thyroid capsule, and group 3 consisted of patients with noninvasive PTC. Results: VEGF expression was noted within the tumor in all groups of PTC patients but was absent in the surrounding normal tissue. Older patients had higher expression of VEGF than younger patients. The age of patients with strong reaction to VEGF was 46 +/- 14 (mean +/- standard deviation), and that in patients with a weaker reaction was 39 +/- 16 (p<0.05). Only 20% of patients with a follicular variant of PTC had a strong reaction to VEGF compared with 68% of patients with classical PTC (p<0.01). Conclusions: VEGF expression appears to be an early event in the development of PTC. Whether VEGF expression promotes the progression of PTC is not known, but the answer to this question may be important in view of its greater expression in older patients, a group whose prognosis in PTC is worse.

Effect of the effluent released from the canine internal mammary artery after intraluminal and extraluminal perfusion of acetylcholine and adenosine diphosphate

Segments of the canine internal mammary artery (35 mm in length) were suspended in vitro in an organ chamber containing physiological salt solution (95% O(2)/5% CO(2), pH = 7.4, 37 degrees C). Segments were individually cannulated and perfused at 5 ml/minute using a roller pump. Vasorelaxant activity of the effluent from the perfused internal mammary arteries was bioassayed by measuring the decrease in tension induced by the effluent of the coronary artery endothelium-free ring which had been contracted with prostaglandin F(2 alpha) (2 x 10(-6) M). Intraluminal perfusion of adenosine diphosphate (10(-5) M) induced significant increase in relaxant activity in the effluent from the perfused blood vessel. However, when adenosine diphosphate (10(-5) M) was added extraluminally to the internal mammary artery, no change in relaxant activity in the effluent was noted. In contrast, acetylcholine produced significant increase in the relaxant activity on the effluent of the perfused internal mammary artery with both intraluminal and extraluminal perfusion. The intraluminal and extraluminal release of endothelium-derived relaxing factor (EDRF) by acetylcholine (10(-5) M) can be inhibited by site-specific administration of atropine (10(-5) M). These experiments indicate that certain agonists can induce the release of EDRF only by binding to intravascular receptors while other agonists can induce endothelium-dependent vasodilatation by acting on neural side receptors.